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Eyeing an expansion of its pain portfolio, Eli Lilly entered the sodium channel inhibitor space on Tuesday through the acquisition of SiteOne Therapeutics. While the upfront amount was not disclosed, the total deal is valued at up to $1 billion, including regulatory and commercial milestones. The takeout comes on the heels of a megaround for SiteOne — and the first FDA approval for a non-opioid pain medication in more than two decades.In December, the biotech raised a $100-million series C, and then in January, Vertex Pharmaceuticals' NaV1.8 inhibitor Journavx (suzetrigine) was greenlit by the US regulator. SiteOne's lead programme, STC-004, also blocks the NaV1.8 sodium channel. The company reported Phase I data in February showing that the compound was well-tolerated with rapid absorption suitable for once-daily oral dosing. Given the pharmacokinetic results, a Phase II trial had been planned to start next half. SiteOne CEO John Mulcahy previously told FirstWord that STC-004 was designed to achieve "the maximum level of efficacy that is possible" by blocking the ion channel. The company is also developing several NaV1.7-targeting programmes, including one partnered with Vertex under a 2022 agreement, as well as STC-002, a topical candidate for ocular surface pain. Given the unmet need, and the potential value, of the non-opioid pain space, SiteOne is one of several startups pursuing sodium channel inhibitors. Latigo Biotherapeutics, which raised a $150-million series B in March, is developing NaV1.8 inhibitors LTG-001 and LTG-305, which are in Phase II testing for acute pain and Phase I for chronic pain, respectively (see – Spotlight On: The pain of success – Vertex’s non-opioid win entices investors to back would-be usurpers).Vertex has pegged Journavx as a multi–billion-dollar product, and during a call with investors earlier this month, management lauded the drug's early rollout (see – Spotlight On: Vertex plots $1B+ sales trajectories for Casgevy, Journavx).Adding to the pipelineWhile Eli Lilly's current pain pipeline doesn't include a NaV channel blocker, it boasts three mid-stage programmes and a bevvy of undisclosed early assets. According to the company's website, three candidates are in Phase II testing for pain: LY3848575, a monoclonal antibody that targets human epiregulin; mazisotine (LY3556050), a small molecule SSTR4 agonist designed to modulate somatostatin signaling, calming nerve excitability and reducing inflammation and pain; and LY3857210, an oral, brain penetrant, small molecule antagonist of the ATP ligand-gated ion channel P2X7."An effective non-opioid treatment remains elusive," said Mark Mintun, Lilly group vice president of neuroscience R&D. "Lilly is eager to continue the development of STC-004."

iStock, Cinefootage Visuals The acquisition of SiteOne provides a bit of diversification for Lilly, which has burrowed into the obesity and diabetes space with mega-blockbuster tirzepatide and several follow-on molecules. Eli Lilly has executed a bolt-on acquisition of SiteOne Therapeutics for up to $1 billion, adding a clutch of non-opioid pain medicines to its pipeline, which has lately been largely focused on obesity and diabetes medications. “Today’s deal adds another arrow to Lilly’s growing quiver of pipeline opportunities, positioning Lilly with advanced planning for diversification and growth beyond GLP-1s,” BMO Capital Markets analysts wrote to investors Tuesday following the announcement. Key to the deal is the Nav1.8 inhibitor STC-004, which is nearing Phase II development for the treatment of pain, according to Lilly’s morning release . The deal could total $1 billion, including an undisclosed upfront payment for additional payments down the line based on certain regulatory and sales milestones. The addition of SiteOne would represent an expansion into new targets for Lilly, but into a field that Vertex Pharma has also captured with the approval of Journavx earlier this year, BMO said. SiteOne has been chasing Vertex in the pursuit of non-addictive pain medications . The pharma earned an FDA approval for suzetrigine , now known as Journavx, in January, marking a significant moment in the treatment of pain. But suzetrigine, which targets the NaV1.8 voltage-gated sodium channel, had a bumpy road through the clinic , with one Phase II trial showing little differentiation between the treatment and placebo arms. Biotechs like SiteOne, Tris Pharma and Latigo Biotherapeutics are hoping to do even better. Lilly, meanwhile, has been taking its own approach to pain with four assets in development. Mazisotine is a SSTR4 agonist in mid-stage testing for adults with diabetic peripheral neuropathic pain. Other Phase II assets include LY3857210, which targets the ATP ligand-gated ion channel P2X7, and LY3848575, a monoclonal antibody, both in chronic pain. The next readout for mazisotine could be coming soon, as the study’s completion date is listed as July. “A long-time player in the pain space, today’s deal reads as a strategic positive for Lilly, fast following a validated mechanism with an attractively priced deal,” BMO wrote. However, the rollout of Vertex’s asset has been challenging, which gave the analysts some pause. The acquisition of SiteOne provides a bit of diversification for Lilly, which has burrowed into the obesity and diabetes space with the mega-blockbuster dual incretin receptor agonist tirzepatide and several follow-on molecules. The deal “appears prudent as Lilly continues its string of pearls approach to deal making following its incretin success,” BMO wrote.